Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019
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Leading a New Paradigm in Cardiovascular Health Management Jefferies 2019 Healthcare Conference June 6, 2019 NASDAQ: AMRN
Forward-Looking Statements and Disclaimer
Forward-looking statements
This presentation contains forward-looking statements, such as those relating to the
commercial potential of Vascepa®, clinical and regulatory efforts and timelines, potential
FDA approvals, intellectual property, cash flow, and other statements that are predictive
in nature and that depend upon or refer to future events or conditions, including financial
guidance and milestones. These statements involve known and unknown risks,
uncertainties and other factors that can cause actual results to differ materially. For
example, as with any study result, further REDUCE-IT™ data assessment and data release
by Amarin and FDA could yield additional useful information to inform greater
understanding of the trial outcome. Investors should not place undue reliance on primary
data or forward-looking statements, which speak only as of the presentation date of this
presentation. Please refer to the “Risk Factors” section in Amarin’s most recent Form 10-Q
filed with the SEC and cautionary statements outlined in recent press releases for more
complete descriptions of risks in an investment in Amarin.
Presentation is for investors (not drug promotion)
This presentation is intended for communication with investors only.
Nothing in this presentation should be construed as promoting the use of Amarin’s
product or product candidates.
2
Amarin Addressing Large Unmet Medical Needs
Problem: cardiovascular (CV) disease is an enormous and worsening
public health burden
Unmet Need: urgent need to help more patients with CV disease; lowering
cholesterol alone is not enough
Solution: Landmark positive CV outcomes trial results of Amarin’s Vascepa®
shows it can effectively and safely lessen this enormous CV health burden
Landmark global outcomes study positions Vascepa to become first drug to cost-
effectively help address residual CV risk beyond cholesterol management
̶ Unprecedented results presented at AHA and published in NEJM in Nov’18
Amarin pursuing expanded label and promotion for Vascepa based on recent
outcomes study results from REDUCE-IT™ trial and sNDA submission
Current Label: Vascepa is already approved for important niche market of treating patients
with very high triglyceride levels >500 mg/dL
Advantage of Being First but Not New: potential cost-effective high share of voice coupled with
existing broad formulary coverage positions Vascepa well for growth in billion dollar market
3
Recent Highlights
sNDA for expanded REDUCE-IT indication accepted by FDA with priority review
PDUFA date of September 28, 2019
Accelerating plans for commercial expansion and launch following assumed FDA approval of Vascepa
as the first therapy for its targeted CV risk reduction indication
67% increase in net total revenue in Q1 2019 compared to Q1 2018
Growth primarily driven by increased volume of Vascepa sales
̶ Increased Vascepa prescription volume from prior prescribers and new prescribers
̶ NRx increase of ~80%, per Symphony Health, in Q1 2019 compared to Q1 2018
American Diabetes Association’s Standards of Medical Care updated to reflect REDUCE-IT results
Recommendation added that icosapent ethyl be considered for patients with diabetes and
atherosclerotic cardiovascular disease or other cardiac risk factors on a statin with controlled LDL-C, but
with elevated triglycerides (135-499 mg/dL) to reduce CV risk
1) Bhatt DL, Steg PG, Miller M, et al. Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT. J Am Coll Cardiol 2019. epub ahead of print.
https://doi.org/10.1016/j.jacc.2019.02.032.
4
Large Need for CV Risk Reduction Beyond Controlled LDL-C
CV Risk
~65%-75% residual CV risk beyond current standard of care1
Controlled LDL-C does not eliminate CV risk
Remaining residual CV risk high even with controlled LDL-C LDL-C
control
25-35%
Cardiovascular Disease: #1 cause of death in the U.S.
>800,000 deaths each year attributable to CV disease;
Residual
more than all cancers combined2 Risk/Unmet Need
Annual treatment cost $555 billion; expected to double 65-75%
within twenty years3, 4
One death every 38 seconds
No FDA approved therapy exists for treating CV risk in dyslipidemia patients beyond LDL-C
~38M patients in U.S. are on statin therapy
>25% of adults in U.S. have CV risk factors beyond LDL-C (e.g. ~50M to 70M adults in U.S.
have elevated triglycerides levels >150 mg/dL)
̶ ~12M of these patients are already on statin therapy
1) Ganda OP, Bhatt DL, Mason RP, Miller M, Boden WE. Unmet need for adjunctive dyslipidemia therapy in hypertriglyderidemia management. J Am Coll Cardiol. 2018. 2) AHA: Heart Disease and Stroke Statistics 2018
At-a-Glance 3) http://www.heart.org/idc/groups/heart-public/@wcm/@adv/documents/downloadable/ucm_491543.pdf 4) Centers for Disease Control and Prevention, https://www.cdc.gov/nchs/fastats/leading-
causes-of-death AHA: Cardiovascular Disease: A Costly Burden for America — Projections through 2035.htm, January, 20, 2017,
5
CV Risk Increases Across TG Levels up to ~150 mg/dL
Above Which Risk Remains but the Relationship Flattens
15%
Dashed lines reflect
95% confidence interval
Predicted CV Risk
10%
In addition to this clinical
data, genetics studies
5% support that TG levels
CV risk begins increasing are as well correlated to
at TG levels
Unprecedented CV Outcomes Position Amarin for Growth
REDUCE-IT cardiovascular outcomes study was robustly conducted
Evaluated Vascepa effects on statin-treated patients with residual elevated TG and other CV risks
̶ Patients had well-controlled baseline LDL-C (median 75 mg/dL) and remained on statin therapy
and other standard of care medications
̶ 8,179 patients randomized 1:1 between Vascepa-arm and placebo-arm
Conducted under a Special Protocol Assessment (SPA) agreement with FDA
>35,000 patient years of study
REDUCE-IT results were positive as per peer reviewed presentations and publications
Primary results based on first occurrence of major adverse cardiovascular events (MACE):
̶ Presented at AHA scientific sessions in Nov 2018
̶ Published in The New England Journal of Medicine (NEJM); the NEJM Journal Watch Cardiology and the
American College of Cardiology recognized REDUCE-IT results as top cardiovascular news for 2018
Total events based on first and recurrent MACE:
̶ Presented at ACC scientific sessions in Mar 2019
̶ Published in Journal of American College of Cardiology
7
Primary Endpoint Achieved in Vascepa Outcomes Study
Largest CV Risk Reduction of Any Drug on Top of Statin Therapy
Endpoint Relative Risk Reduction (RRR) P-value
on top of statin therapy
Primary Endpoint (5-point MACE) ↓ 25% 0.00000001
Key Secondary Endpoint (3-point “Hard” MACE) ↓ 26% 0.0000006
CV Death ↓ 20% 0.03
Heart Attack (Fatal or Nonfatal) ↓ 31% 0.000005
Stroke (Fatal or Nonfatal) ↓ 28% 0.01
“This may be the biggest development in cardiovascular prevention since statins.”
- Deepak L. Bhatt, MD, MPH
Professor of Medicine at Harvard Medical School
Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital Heart and Vascular Center
Global Principal Investigator and Steering Committee Chair for REDUCE-IT
- Brigham and Women’s REDUCE-IT results press release November 10, 2018
MACE = major adverse cardiovascular events
8
CV Event Curve for Primary Endpoint Separated at ~1 Year
and Remained Separated Throughout Follow-up Period
30
28.3%
Hazard Ratio, 0.75
Patients with an Event (%)
20 (95% CI, 0.68–0.83)
Placebo
23.0% RRR = 24.8%
ARR = 4.8%
NNT = 21 (95% CI, 15–33)
Vascepa (icosapent ethyl)
10
P=0.00000001
0
0 1 2 3 4 5
Years since Randomization
CV event curve for key secondary endpoint (3-point MACE), not shown here, separated
prior to 2 years and remained separated throughout follow-up period
Bhatt DL, Steg PG, Miller M, et al. N Engl J Med. 2018.
9
MACE Continues to be REDUCED Beyond 1st Events
(25%, 32%, 31% and 48% for 1st, 2nd, 3rd and 4th Events, Respectively)
RR 0.70 30% Reduction in Total Events
(95% CI, 0.62-0.78) Average ~1 Fewer Event per 6 Patients
P=0.00000000036 Treated with Icosapent Ethyl for 5 years
1,546
1,600
≥4 Events
Number of Primary Composite Endpoint Events
126 No. of
RR 0.52 Fewer
1,400
143 (95% CI, 0.38-0.70) Events
1,200 3rd Events 1,076 -470
HR 0.69
376 (95% CI, 0.59-0.82) 63 -63
1,000 72 -71
2nd Events
800 HR 0.68 236 -140
(95% CI, 0.60-0.78)
600
901
400 1st Events
HR 0.75 705 -196
(95% CI, 0.68-0.83)
200 P=0.000000016
0
Placebo Icosapent Ethyl
[N=4090] [N=4089]
Reduced Dataset Event No. 1st 2nd 3rd ≥4 RR= rate ratio
HR= hazard ratio
Bhatt DL, Steg PG, Miller M, et al. J Am Coll Cardiol. 2019.
10Total (First and Subsequent) Events
Key Secondary Endpoint (3 Point “Hard” MACE: CV Death, MI, Stroke)
Key Secondary Composite Endpoint
0.3 Total Events:
Placebo: Total Events
RR, 0.72
Icosapent Ethyl: Total Events
Cummulative Events per Patient
(95% CI, 0.63–0.82)
Placebo: First Events
Icosapent Ethyl: First Events P=0.00000071
0.2 Primary (1st) Events:
HR, 0.74
(95% CI, 0.65–0.83)
P=0.0000006
0.1
0.0
0 1 2 3 4 5
Years since Randomization
RR= rate ratio
HR= hazard ratio
Bhatt DL, Steg PG, Miller M, et al. J Am Coll Cardiol. 2019.
11Additional Important Results from REDUCE-IT
Vascepa®
Positive results consistent across multiple subgroups including
REDUCE-IT3
Male/female 2018
Diabetes/no diabetes
Secondary/primary prevention cohorts 20%
CV Death3
Number needed to treat (NNT): 21 for primary endpoint
Low NNT combined with affordable price of Vascepa
should support continued broad managed care coverage 25%
For context, NNTs for other notable, but not competitive with RRR MACE3
Vascepa, drugs:
̶ Atorvastatin (Lipitor®)1: 45
̶ Evolocumab (Repatha®)2: 67
• No head-to-head study with these drugs 21 NNT3
• Study periods and study populations differ
~1 fewer MACE per 6 patients treated in total event analysis4
Result should be helpful in pharmacoeconomic analysis
1) LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352: 1425–35. 2) Sabatine MS, Giugliano RP, Keech AC, et al.
Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713. 3) Bhatt DL, Steg PG, Miller M, et al. N Engl J Med. 2018. 4) Bhatt DL, Steg PG, Miller M, et al. Effects of Icosapent
Ethyl on Total Ischemic Events: From REDUCE-IT. J Am Coll Cardiol 2019. epub ahead of print. http://doi.org/10.1016/2019/03/01/j.jacc.2019.02.032
12Robust CV Risk Reduction Independent of TG Levels
Reduction of CV events was similar for patients with TG levels above and below 150 mg/dL
~10% of patients enrolled had TG levelsVascepa Well Tolerated with Safety Profile Consistent with
Omega-3 Fatty Acids and Current FDA Labelling
Overall adverse event rates in REDUCE-IT were similar across the statin plus Vascepa and the
statin plus placebo treatment groups
Overall patient population had numerous events reflecting their at-risk condition and need
for medical care
No significant differences between treatments in the overall rate of treatment-emergent
adverse events or serious adverse events leading to withdrawal of study drug
No Serious Adverse Event (SAE) >2% frequency and greater in Vascepa-arm
Adverse Events (AE) greater in the Vascepa-arm, included:
Peripheral edema (6.5% Vascepa-arm; 5.0% placebo-arm), atrial fibrillation (5.3% Vascepa-
arm; 3.9% placebo-arm) and serious bleeding (2.7% Vascepa-arm; 2.1% placebo-arm)
These events did not appear associated with increased MACE or other major issues
̶ Peripheral edema increased without increase in heart failure
̶ AFib increased but heart attack, cardiac arrest and sudden death each decreased >30%
̶ Bleeding rates were characterized as low; no fatal bleeding assessed by investigators as related
to Vascepa; no significant increases in hemorrhagic stroke, CNS bleeding or GI bleeding
Bhatt DL, Steg PG, Miller M, et al. N Engl J Med. 2018.
1425% RRR on Top of Controlled LDL-C is Landmark Result
Relative Risk Positive Peak Net
Class CVOT
Reduction (RRR) CVOT Sales in U.S.
STATIN THERAPY
Statins Various 25-35% √ >$20B - 2016
OTHER LDL-CHOLESTEROL LOWERING DRUGS ON TOP OF STATIN THERAPY
Cholesterol Absorption Inhibitors IMPROVE-IT 6% √ $1.8B - 2007
FOURIER 15%
PCSK9 Inhibitors √ Recently Launched
ODYSSEY 15%
OTHER DRUGS ON TOP OF STATIN THERAPY
Anti-Inflammatory CANTOS 15% √ N/A
Omega-3 Mixture (Lovaza 1g/d) ASCEND/VITAL Not Significant X $1.0B - 2013
EPA (Epadel) JELIS 19% √ N/A (in Japan only)
EPA (Vascepa) REDUCE-IT 25% √ TBD
25% RRR with Vascepa is largest of any therapy on top of statins
Many other therapies failed trying to lower CV risk (e.g. CETP inhibitors, fibrates, niacin)
Lipitor (atorvastatin) lowers CV risk ~25%; REDUCE-IT effect is incremental to statins
15Science of Lipid Management and Clinical Effects of Omega-3
Fatty Acids Are Complex
Vascepa is unique proven prescription therapy developed over 10 years at cost of >$500M
Single active ingredient EPA (eicosapentaenoic acid)
Unique omega-3 molecule1 derived from nature
̶ New chemical entity designation by FDA for Vascepa as pure EPA
̶ Purity achieved while overcoming the fragility and stability issues associated with omega-3s
Excludes saturated fats, omega-6s and other components in fish oil
No known drug-drug interactions1
EPA is smaller than DHA in length and number of double bonds that influence activities
Small molecule capable of entering and improving function of endothelial cells
Doesn’t inhibit clearance of LDL-C like DHA (docosahexaenoic acid)
Omega-3s are easily oxidized or otherwise damaged
Vascepa is expertly manufactured and encapsulated
Demonstrated multi-year stability with consistent reproducibility
1
See Vascepa® {package insert}. Bedminster, NJ: Amarin Pharma Inc.; 2017
16Mechanistic Effects of Vascepa’s Active Ingredient on Multiple
Atherosclerotic Processes Beyond Lipid Modification
Multiple Processes Potentially Affected by EPA1
Endothelial function Inflammation/cytokines Plaque formation/progression
Oxidative stress Platelet aggregation
Foam cell formation Thrombus formation
Plaque rupture
The extent to which these or other pleiotropic effects of EPA may have contributed to the success of
Vascepa in the REDUCE-IT study relative to other effects of EPA (e.g. lipid lowering) is under evaluation
1. Borow KM et al. Atherosclerosis. 2015;242(1):357-366
17Commercial Expansion Aligns with Improved Patient Care
Priority focus on large U.S. market opportunity
Transforming from niche to large outcomes-based opportunity
Market experience provides foundation for growth
Managed care coverage already broad
>5M Rx for Vascepa since launched for niche market in 2013
Expanding Vascepa promotion in 2019
Expanded U.S. physician targets from ~20k to >50k
Initial feedback from healthcare professionals regarding REDUCE-IT
results broadly positive with new prescribers increasing
Targeted promotion based on Amarin’s First Amendment decision
and related FDA agreement reached in 2016 regarding
communication of truthful and non-misleading information to
healthcare professionals
̶ Expand promotion further following label expansion
Vascepa promotion to expand further following label expansion
Current promotion is qualified and limited, particularly to consumers
18Preparing for Growth
Strengthening relationships
Building relationships with KOLs and industry groups
̶ 24 scientific publications/posters supported in early 2019 and >40 in 2018
̶ Active in medical education programs and other forms of educational and promotional outreach
Supply capacity expanding
Multiple proven suppliers for Vascepa
─ Evaluating options to expand capacity to support multiple billions of dollars in revenue
Sustainable business
Vascepa patents listed in the FDA’s Orange Book expire in 2030
─ Teva, by agreement, may launch generic in August 2029
NCE protection
International expansion
Middle East: Partner obtained approved for Vascepa sales in Lebanon and United Arab Emirates with
applications in other countries under review
Canada: Partner received priority review from Health Canada for Vascepa; NDS seeking Vascepa label
based on REDUCE-IT submitted to Health Canada on Apr 26, 2019
China: Regulatory approval for Vascepa being pursued via ongoing clinical study
Europe: Aiming before the end of 2019 to submit application seeking approval for Vascepa
Other geographies: opportunities being pursued
19Evolution of Preventative Cardiovascular Care
Before statin therapy Focus on LDL-C
STATINS
Pre-Statins
PCSK9s
Cholesterol Ezetimibe
Resins
After statin therapy, ~25% RRR on top of statins
modification of other lipid markers
have not lowered CV risk
Fibrates,
VASCEPA®
Niacin,
Omega-3
Mixtures
20Capitalization Summary (Millions)
As of March 31, 2019
Cash and Cash Equivalents $211
Debt Obligations
NOTES $ - None
ROYALTY-BEARING INSTRUMENT1 $81 10% of revenues until fully paid; no maturity date
Common Stock and Equivalent Shares
COMMON/PREFERRED SHARES2 360 Preferred shares mirror common but non-voting
OPTIONS AND RESTRICTED STOCK 26
TOTAL IF ALL EXERCISED 386
Tax Jurisdiction (primary) Ireland Loss carryforwards of ~$800
1 Representsface value of debt balance remaining to be paid in cash; a slightly lower carrying value is reported for accounting
purposes in accordance with U.S. GAAP
2 Includes 29 million common share equivalents issuable upon conversion of preferred shares
21Leading a New Paradigm in Cardiovascular Health Management Jefferies 2019 Healthcare Conference June 6, 2019 NASDAQ: AMRN
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